Pleomorphic Liposarcoma Unraveled: Investigating Histopathological and Immunohistochemical Markers for Tailored Diagnosis and Therapeutic Innovations.

Liposarcomas are some of the most challenging soft tissue tumors and are subclassified into multiple subtypes with special histologic and molecular features. The peculiarities of each histopathological subtype influence the clinical behavior, management, and treatment of these neoplasms. For instance, well-differentiated liposarcomas are common soft tissue malignancies and usually display a favorable outcome. On the other hand, pleomorphic liposarcoma is the rarest, yet the most aggressive subtype of liposarcoma. This histopathological diagnosis may be challenging due to the scarce available data and because pleomorphic liposarcomas can mimic other pleomorphic sarcomas or other neoplasms of dissimilar differentiation. Nevertheless, the correct diagnosis of pleomorphic liposarcoma is of utmost importance as such patients are prone to develop local recurrences and metastases. Treatment usually consists of surgical excision along with radiotherapy and follow-up of the patients. Therefore, this review aims to assess the complex clinical, histological, and immunohistochemical features of liposarcomas in order to establish how these characteristics influence the management and prognosis of the patients, emphasizing the particularities of pleomorphic liposarcoma.

Genomic Insights into the Role of TOP Gene Family in Soft-Tissue Sarcomas: Implications for Prognosis and Therapy.

This study focuses on the role of topoisomerases (TOPs) in sarcomas (SARCs), highlighting TOPs' influence on sarcoma prognosis through mRNA expression, genetic mutations, immune infiltration, and DNA methylation analysis using transcriptase sequencing and other techniques. The findings indicate that TOP gene mutations correlate with increased inflammation, immune cell infiltration, DNA repair abnormalities, and mitochondrial fusion genes alterations, all of which negatively affect sarcoma prognosis. Abnormal TOP expression may independently affect sarcoma patients' survival. Cutting-edge genomic tools such as Oncomine, gene expression profiling interactive analysis (GEPIA), and cBio Cancer Genomics Portal (cBioPortal) are utilized to explore the TOP gene family (TOP1/1MT/2A/2B/3A/3B) in soft-tissue sarcomas (STSs). This in-depth analysis reveals a notable upregulation of TOP mRNA in STS patients arcoss various SARC subtypes, French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) grades, and specific molecular profiles correlating with poorer clinical outcomes. Furthermore, this investigation identifies distinct patterns of immune cell infiltration, genetic mutations, and somatic copy number variations linked to TOP genes that inversely affect patient survival rates. These findings underscore the diagnostic and therapeutic relevance of the TOP gene suite in STSs.

Outcomes of non-angiosarcoma radiation-associated soft tissue sarcomas of the chest.

BACKGROUND: Radiation-associated soft tissue sarcomas (RA-STS) are rare complications of patients receiving radiation therapy (RT) and are generally associated with a poor prognosis. Most of the literature surrounding RA-STS of the chest is centered on angiosarcoma. Therefore, we aim to document the management and outcome of patients with non-angiosarcoma RA-STS of the chest. METHODS: We reviewed 17 patients (all female, median age 65 years) diagnosed with RA-STS. The most common primary malignancy was breast carcinoma (n = 15), with a median RT dose of 57.9 Gy. All patients underwent surgical resection; five patients (29%) received radiotherapy; and five patients (29%) received peri-operative chemotherapy. RESULTS: The 5-year local recurrence and metastatic-free survival were 61% and 60%, while the 5-year disease-specific survival was 53%. Local recurrence was associated with death due to disease (HR 9.06, p = 0.01). Complications occurred in nine of patients, most commonly due to a wound complication (n = 7). At the most recent follow-up, the median Musculoskeletal Tumor Society Score was 63%. CONCLUSION: RA-STS involving the chest wall are aggressive tumors with a high risk of local relapse and death due to disease. Local recurrence was associated with death due to disease; as such, we recommend aggressive surgical management with evaluation for adjuvant therapies.

Clinical features and outcomes of young patients with low-grade non-rhabdomyosarcoma soft tissue sarcomas treated with a risk-based strategy: A report from Children's Oncology Group study ARST0332.

BACKGROUND: In retrospective analyses, the Pediatric Oncology Group [POG) and the Federation National des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade predict outcome in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), but prospective data on grading, clinical features, and outcomes of low-grade NRSTS are limited. METHODS: We analyzed patients less than 30 years of age enrolled on Children's Oncology Group (COG) study ARST0332 (NCT00346164) with POG grade 1 or 2 NRSTS. Low-risk patients were treated with surgery alone. Intermediate-/high-risk patients received ifosfamide/doxorubicin and radiotherapy, with definitive resection either before or after 12 weeks of chemoradiotherapy. RESULTS: Estimated 5-year event-free and overall survival were 90% and 100% low risk (n = 80), 55% and 78% intermediate risk (n = 15), and 25% and 25% high risk (n = 4). In low-risk patients, only local recurrence was seen in 10%; none with margins greater than 1 mm recurred locally. Sixteen of 17 intermediate-/high-risk patients who completed neoadjuvant chemoradiotherapy underwent gross total tumor resection, 80% with negative margins. Intermediate-/high-risk group events included one local and seven metastatic recurrences. Had the FNCLCC grading system been used to direct treatment, 29% of low-risk (surgery alone) patients would have received radiotherapy ± chemotherapy. CONCLUSIONS: Most low-risk patients with completely resected POG low-grade NRSTS are successfully treated with surgery alone, and surgical margins greater than 1 mm may be sufficient to prevent local recurrence. Patients with intermediate- and high-risk low-grade NRSTS have outcomes similar to patients with high-grade histology, and require more effective therapies. Use of the current FNCLCC grading system may result in overtreatment of low-risk NRSTS curable with surgery alone.

Treatment and outcomes in pediatric inflammatory myofibroblastic tumors - A systematic review of published studies.

Inflammatory myofibroblastic tumor (IMT) is a soft tissue neoplasm which can be locally invasive, recur, or in rare cases metastasize. Often originating from the abdomen or thorax, IMT most commonly affects children and young adults. Due to its rarity comprehensive reports detailing clinical management and outcome(s) are sparse and often based on limited index case numbers. This study systematically analyzes outcome metrics of pediatric IMT and identifies risk factors for mortality. Medline/Embase databases were searched in accordance with PRISMA guidelines. Final analysis included 57 studies with 673 IMT patients (355 males, 53 %). Individual patient data was available for 405 cases with a median follow-up period of 36 months. Tumor sites included abdomen/pelvis (n = 233, 58 %), thorax (n = 125, 31 %), head/neck (n = 34, 8 %), and extremities (n = 13, 3 %). Surgical tumor resection was the mainstay of treatment, while only 20 patients (5 %) were treated non-operatively. Recurrence(s) were reported in 80 patients (20 %) with 34 (12 %) requiring reoperation. Positive tumor margins were a significant risk factor for tumor recurrence (p < 0.0001). Chemo/radiotherapy was reported in 98 patients (25 %). Most patients (94 %) survived; 81 % (n = 237) with no evidence of recurrent disease, 14 % (n = 41) were alive with disease, and 25 (6 %) died of disease. Positive margins at primary operation, and metastatic disease were associated with mortality (p < 0.0001 for both). IMT is a rare tumor with favorable outcome for the majority of patients. Whilst most patients will present with benign tumors, complete surgical resection (R0) is crucial, as positive surgical margins are a significant risk factor for tumor recurrence and mortality.

Myxoid Inflammatory Myofibroblastic Sarcoma: Clinicopathologic Analysis of 25 Cases of a Distinctive Sarcoma With Deceptively Bland Morphology and Aggressive Clinical Behavior.

The number of recognized sarcoma types harboring targetable molecular alterations continues to increase. Here we present 25 examples of a distinctive myofibroblastic tumor, provisionally termed "myxoid inflammatory myofibroblastic sarcoma," which might be related to inflammatory myofibroblastic tumor, and which occurred in 13 males (52%) and 12 females at a median age of 37 years (range: 7 to 79 years). Primary tumor sites were peritoneum (18 patients; 72%), paratesticular (2; 8%), chest wall (1), upper extremity (1), esophagus (1), retroperitoneum (1), and uterus (1). Nine peritoneal tumors (50%) were multifocal at presentation; all other tumors were unifocal. Tumors showed bland-to-mildly-atypical neoplastic myofibroblasts in a myxoid stroma, with prominent inflammatory infiltrates in 22 cases (88%). Most tumors showed delicate branching stromal vessels like those of myxoid liposarcoma, and most showed infiltrative growth through non-neoplastic tissue. Immunohistochemistry demonstrated expression of SMA (19/25 tumors; 76%), desmin (13/22; 59%), and CD30 (5/11; 45%), while ALK was expressed in 1 tumor (of 25; 4%) that was negative for ALK rearrangement. Sequencing of 11 tumors showed seven to harbor tyrosine kinase fusions (4 PDGFRB , 2 PML :: JAK1 , 1 SEC31A :: PDGFRA ). Two instead harbored hot spot KRAS mutations (G12V and Q61H), and 2 were negative for known driving alterations. Clinical follow-up was available for 18 patients (72%; median: 2.7 years; range: 4 mo-12.3 years). Nine patients (50%) were alive with no evidence of disease, 5 (28%) died of disease, and 4 (22%) were alive with disease. Seven patients (39%) experienced peritoneal relapse or distant metastasis. Two patients showed disease progression on conventional, nontargeted chemotherapy. The patient whose tumor harbored SEC31A :: PDGFRA was treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.

Establishing biomarkers for soft tissue sarcomas.

INTRODUCTION: Soft tissue sarcomas (STS) are a rare and diverse group of tumors. Curative options are limited to localized disease, with surgery being the mainstay. Advanced stages are associated with a poor prognosis. Currently, the prognosis of the patient is based on histological classification and clinical characteristics, with only a few biomarkers having entered clinical practice. AREAS COVERED: This article covers extensive recent research that has established novel potential biomarkers based on genomics, proteomics, and clinical characteristics. Validating and incorporating these biomarkers into clinical practice can improve prognosis, prediction of recurrence, and treatment response. Relevant literature was collected from PubMed, Scopus, and clinicaltrials.gov databases (November 2023). EXPERT OPINION: Currently, defining prognostic markers in soft tissue sarcomas remains challenging. More studies are required, especially to personalize treatment through advanced genetic profiling and analysis using individual tumor and patient characteristics.

Tumours of the foot: A 10 years retrospective analysis.

INTRODUCTION: The foot is a complex structure composed of several tissues, each of which can be the origin of the proliferation and development of the tumour. Most lesions about the foot are reactive or inflammatory, but some are true neoplasms. METHOD: This is a retrospective analysis of 4997 patient records treated in the Orthopaedic Oncology Unit of University Malaya Medical Centre, Malaysia, between 1 January 2010 to 31 December 2020. Demographic data of 195 patients with foot tumours were analysed out of 4997 neoplasm patients. RESULTS: There were 195 cases of foot tumours: 148 were benign, and 47 were malignant. 47 were bone tumours, 4 were metastases, and 144 were soft tissue tumours. Six patients succumbed to the disease, two cases of giant cell tumour (GCT) and one patient with synovial sarcoma had a recurrence. Treatment of foot tumours was wide resection in general. However, in metastasis cases, amputation was done. The majority of tumours were in the toes and dorsum of the foot. Soft tissue tumours of the foot occur in the elderly population in contrast to bone tumours, mainly in the second decade of life. The gender distribution was almost equal for foot tumours. Ganglion and Giant Cell Tumour of the bone are the commonest benign soft tissue and bone tumours. The most common malignant soft tissue and bone tumours are malignant melanoma and chondrosarcoma. The amputation rate is 5.64% the recurrence rate is 1.54%. Mortality rate is 3.08%. The MSTS score is 79%, and the TESS score is 76.23%. CONCLUSION: Foot tumours are relatively rare, mostly originating from soft tissue and exhibiting a benign nature. Nonetheless, a noteworthy proportion-approximately a quarter of these tumours-demonstrate malignancy. The surgical interventions undertaken in managing these tumours and associated functional outcomes generally yield acceptable results.

Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS. METHODS: From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at seven academic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR), time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed. RESULTS: Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLR recurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation. CONCLUSION: For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

The Effect of chemo- and radiotherapy on tumor necrosis in soft tissue sarcoma- does it influence prognosis?

BACKGROUND: Soft tissue sarcomas (STSs) are a heterogeneous group of tumors. Wide surgical resection is standard, often combined with neoadjuvant chemotherapy, radiotherapy, or both. Studies have shown the predictive value of tumor necrosis in bone sarcoma (BS); however, the role of necrosis in STS after neoadjuvant therapies is still unclear. This study aimed to investigate the role of chemo- and radiotherapy in the formation of tumor necrosis and to evaluate the influence of tumor necrosis on overall survival and local recurrence-free survival. Data from BS patients and patients who did not receive neoadjuvant therapy were compared. METHODS: A total of 779 patients with STS or BS were treated surgically. In all patients, tumor-specific factors such as type, size, or grading and the type of adjuvant therapy were documented. Local recurrence (LR), the diagnosis of metastatic disease, and survival during follow-up were evaluated. RESULTS: A total of 565 patients with STS and 214 with BS were investigated. In STS, 24.1% G1 lesions, 34.1% G2 lesions, and 41.8% G3 lesions were observed. Two hundred twenty-four of the patients with STS and neoadjuvant therapy had either radiotherapy (RTx) (n = 80), chemotherapy (CTx) (n = 93), or both (n = 51). Three hundred forty-one had no neoadjuvant therapy at all. In STS, tumor necrosis after neoadjuvant treatment was significantly higher (53.5%) than in patients without neoadjuvant therapy (15.7%) (p < 0.001). Patients with combined neoadjuvant chemo-/radiotherapy had substantially higher tumor necrosis than those with radiotherapy alone (p = 0.032). There was no difference in tumor necrosis in patients with combined chemo-/radiotherapy and chemotherapy alone (p = 0.4). The mean overall survival for patients with STS was 34.7 months. Tumor necrosis did not influence survival in a subgroup of G2/3 patients. In STS with no neoadjuvant therapy and grading of G2/3, the correlation between necrosis and overall survival was significant (p = 0.0248). There was no significant correlation between local recurrence (LR) and necrosis. CONCLUSION: STS shows a broad spectrum of necrosis even without neoadjuvant chemo- or radiotherapy. After CTx or/and RTx necrosis is enhanced and is significantly pronounced with a combination of both. There is a trend toward higher necrosis with CTx than with RTx. Grading substantially influences the necrosis rate, but necrosis in soft-tissue sarcoma following neoadjuvant therapy does not correlate with better survival or a lower local recurrence rate, as in bone sarcomas.

Demographic and clinical profile of 1106 adult soft tissue sarcoma patients: A single institutional prospective database experience from India.

BACKGROUND: Adult soft tissue sarcomas (STS) are rare and diverse. Current management is based on limited literature from the West. Therefore, data from different geographical regions is required, including the low-middle-income countries. This is our experience managing adult sarcomas in the tertiary cancer center of North India. MATERIALS AND METHODS: This is a retrospective analysis of the structured sarcoma database of patients treated in the surgical oncology department between 1992 and 2020. The descriptive analysis includes demography, site distribution, diagnosis, histopathology variations, prior surgical interventions, and stage. RESULTS: A total of 1106 soft tissue sarcoma patients were treated in three decades. Age distribution was 13%, 43%, 31%, and 11% in <20, 21-40, and 41-60 and >60 years, respectively. The male-to-female ratio was 1.73. The anatomical distribution was 17%, 42%, 23%, 7%, 7%, and 3% in upper extremity, lower extremity, trunk, retroperitoneum, head and neck, and viscera, respectively. Overall, 49% of patients had undergone prior suboptimal surgeries at community hospitals. Common histology subtypes were synovial sarcoma (18%), undifferentiated pleomorphic sarcoma (UPS) (13%), dermatofibrosarcoma protuberans (12%), and liposarcoma (9%). A pathological discordance of 13% was identified between the initial and the final histologies. Overall, 61% of tumors were high-grade. Memorial Sloan Kettering Stages II and III were present in 33% and 35% of patients, respectively. CONCLUSIONS: This is one of the largest single institutional experiences of STS from the Asian population. Mostly young adults were affected with male preponderance. The lower extremity and trunk were common subsites. Frequent histologies were synovial sarcoma and UPS. A high rate of suboptimal surgical intervention at the community level and pathological discordance was noted. This study highlights the need to establish prospective structured databases for capturing quality information related to rare malignancies and providing insights for future research.

Primary soft tissue sarcoma breast with multiphenotypic differentiation.

Primary soft tissue sarcomas of the breast are rare aggressive neoplasms. These often are misdiagnosed with other more common neoplasms like fibroepithelial malignancies, namely phyllodes tumour and metaplastic carcinoma. Being uncommon, chances of being misdiagnosed are higher leading to early mortality. A multidisciplinary team incorporating surgery, pathology, chemotherapy and radiotherapy is required to formulate an approach to primary soft tissue sarcoma. Generally, these tumours may show single or dual phenotype; we present one rare case report showing multiphenotypic differentiation.

Neoadjuvant Chemotherapy in High-Grade Myxoid Liposarcoma: Results of the Expanded Cohort of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish Sarcoma Groups (PSG).

PURPOSE: A randomized trial was conducted to compare neoadjuvant standard (S) anthracycline + ifosfamide (AI) regimen with histology-tailored (HT) regimen in selected localized high-risk soft tissue sarcoma (STS). The results of the trial demonstrated the superiority of S in all STS histologies except for high-grade myxoid liposarcoma (HG-MLPS) where S and HT appeared to be equivalent. To further evaluate the noninferiority of HT compared with S, the HG-MLPS cohort was expanded. PATIENTS AND METHODS: Patients had localized high-grade (cellular component >5%; size ≥5 cm; deeply seated) MLPS of extremities or trunk wall. The primary end point was disease-free survival (DFS). The secondary end point was overall survival (OS). The trial used a noninferiority Bayesian design, wherein HT would be considered not inferior to S if the posterior probability of the true hazard ratio (HR) being >1.25 was <5%. RESULTS: From May 2011 to June 2020, 101 patients with HG-MLPS were randomly assigned, 45 to the HT arm and 56 to the S arm. The median follow-up was 66 months (IQR, 37-89). Median size was 107 mm (IQR, 84-143), 106 mm (IQR, 75-135) in the HT arm and 108 mm (IQR, 86-150) in the S arm. At 60 months, the DFS and OS probabilities were 0.86 and 0.73 (HR, 0.60 [95% CI, 0.24 to 1.46]; log-rank P = .26 for DFS) and 0.88 and 0.90 (HR, 1.20 [95% CI, 0.37 to 3.93]; log-rank P = .77 for OS) in the HT and S arms, respectively. The posterior probability of HR being >1.25 for DFS met the Bayesian monitoring cutoff of <5% (4.93%). This result confirmed the noninferiority of trabectedin to AI suggested in the original study cohort. CONCLUSION: Trabectedin may be an alternative to standard AI in HG-MLPS of the extremities or trunk when neoadjuvant treatment is a consideration.

Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study.

BACKGROUND: Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy. METHODS: This retrospective, multicenter study included therapy naïve patients with D-TGCT from eight sarcoma centers worldwide between 2000 and 2019. Patients initially managed by active surveillance following their first consultation were eligible. Data regarding the radiological and clinical course and subsequent treatments were collected. RESULTS: Sixty-one patients with primary D-TGCT were initially managed by active surveillance. Fifty-nine patients had an MRI performed around first consultation: D-TGCT was located intra-articular in most patients (n = 56; 95 %) and extra-articular in 14 cases (24 %). At baseline, osteoarthritis was observed in 13 patients (22 %) on MRI. Most of the patients' reported symptoms: pain (n = 43; 70 %), swelling (n = 33; 54 %). Eight patients (13 %) were asymptomatic. Follow-up data were available for 58 patients; the median follow-up was 28 months. Twenty-one patients (36 %) had radiological progression after 21 months (median). Eight of 45 patients (18 %) without osteoarthritis at baseline developed osteoarthritis during follow-up. Thirty-seven patients (64 %) did not clinically deteriorate during follow-up. Finally, eighteen patients (31 %) required a subsequent treatment. CONCLUSION: Active surveillance can be considered adequate for selected therapy naïve D-TGCT patients. Although follow-up data was limited, almost two-thirds of the patients remained progression-free, and 69 % did not need treatment during the follow-up period. However, one-fifth of patients developed secondary osteoarthritis. Prospective studies on active surveillance are warranted.